The major project in the laboratory is to determine pathogenetic mechanisms involved in the development of paraffin oil (Pristane) induced plasmacytomas in BALB/c mice. BALB/cAn mice are highly susceptible to developing these tumors while most other strains are resistant. Over 95% of plasmacytomas induced by pristane have chromosomal translocations (rcpt(12;15), rcpt(6;15)) involving directly or indirectly the c-myc locus on chr 15. We have developed model genetic systems for finding the genetic basis of susceptibility and resistance to plasmacytoma development by using BALB/cAn.DBA/2 (C.D2) and BALB/cAn.BALB/cJ (C.J) congenics. Three genes have been identified that confer partial resistance: Pctr- 1 (Fv-1, chr 4), Pctr-2 (Ly-6, chr 15) and Pctr-3 (Qa2, chr 17). Congenic mice constructed by combining these genes have produced even stronger resistance. In collaboration with Dr. K. Sanford, we have found genes associated with DNA repair deficiencies in BALB/cAn mice and C.D2 congenics: Rep-1 (Pep-3, chr 1) and Rep-2 (Fv-1, chr 4). Rep-2 and Pctr-1 could be the same gene. The linkage of Pctr-2 to Ly-6, c-myc Mupm-1 (MUP modifier) and Afr-1 (regulator of alpha fetoprotein) has been established. Plasmacytomas can be induced with short latent periods in BALB/cAn mice by the infection of pristane conditioned mice with retroviruses containing oncogenes. Our recent studies demonstrate the potent cooperative action of myc and ras (in a collaboration with K. Marcu, Stony Brook). (BALB/c x DBA/2)F1 hybrids injected with RIM virus (containing c-myc and v-Ha-ras) and pristane are highly susceptible to plasmacytoma induction, indicating the existence of a dominant gene of BALB/c origin that confers susceptibility.